Recent reports indicate that several mechanisms may operate independently or jointly in the induction and maintenance of acquired immunological tolerance, and that one may predominate over the other depending on various factors such as: 1) the age of the host at the time of the induction of tolerance, 2) the stage of differentiation of the lymphocytes at the time of induction of tolerance, and 2) the nature of the antigen in question. In additon there is evidence that certain clones of B-cells are preferentially suppressed or eliminated during the induction of tolerance. It is the purpose of this project to: 1) define the mechanism of the induction of specific tolerance in neonatal mice to human gamma globulin and to the hapten azobenzenearsonate; 2) to determine the mechanism of the induction of tolerance to azobenzene arsonate in adult mice: 3) to determine the relative effect of tolerance induction on the expression and recovery of individual B-cell clones; and 4) to determine the nature of the genetic information expressed after the spontaneous loss of tolerance. BIBLIOGRAPHIC REFERENCES: Halsey, J.F., and D.C. Benjamin. 1976. Induction of Tolerance in Nursing Neonates by Absorption of Tolerogen from Colostrum. J. Immunol. 116:1204. Teale, J.M., and D.C. Benjamin. 1976. Antibody as a Specific Probe for Studying the Refolding of Bovine Serum Albumin. I. The Catalysis of Reoxidation of Reduced Bovine Serum Albumin by Glutathione and a Disulfide Interchange Enzyme. J. Biol. Chem. 251:4603.